The following description of the background of the present technology is provided simply as an aid in understanding the present technology and is not admitted to describe or constitute prior art to the present technology.
Disorders of the inner ear comprise the largest and most serious class of diseases responsible for hearing loss, with 250 million people worldwide suffering from disabling hearing loss (Holley M C, Drug Discov Today 10(19):1269-82 (2005)). In the United States alone, 28 million patients suffer from sensorineural hearing loss (SNHL), a condition that currently causes an irreversible decline in cochlear function, and profound deafness remains the most prevalent serious medical condition at birth, with 3 in 1000 newborns suffering from this condition. In addition to these auditory disorders, tinnitus remains an intractable problem for many patients.
The principal challenge in treatment of inner ear diseases remains the inaccessibility of targets for therapy, due largely to the presence of the blood-cochlear barrier. Oral medications are typically blocked by the blood-cochlear barrier. Intratympanic delivery of compounds for treatment of inner ear diseases relies upon diffusion through the round window membrane (RWM), a structure with widely disparate transport properties depending upon the patient and disease state. This variability results in poor dosage control, and coupled with the reliance on passive diffusion mechanisms to transport drugs along the length of the cochlea, has limited the effectiveness of intratympanic delivery. See Borenstein J., Expert Opin Drug Deliv. 8(9):1161-1174 (2011).